Funded by:FL and AJ were supported, respectively, by grants PI14/00931 and PI15/00974, from Instituto de Salud Carlos III, MINECO and Feder Funds and by S2010/BMD-2359 from
Comunidad de Madrid. MDR was supported by grant S2010/BMD-2420 from Comunidad
de Madrid and SAF2013-43475-R from MINECO. AZ was supported by S2010/BMD-2359 from Comunidad de Madrid

Abstract:

PDT is widely applied for the treatment of non-melanoma skin cancer premalignant
and malignant lesions (actinic keratosis, basal cell carcinoma and in
situ squamous cell carcinoma). In photodynamic therapy (PDT) the interaction
of a photosensitizer (PS), light and oxygen leads to the formation of reactive
oxygen species (ROS) and thus the selective tumor cells eradication. Xeroderma
pigmentosum (XP) and Gorlin-Goltz Syndrome (GS) patients are at high risk of
developing skin cancer in sun-exposed areas. Therefore, the use of PDT as a
preventive treatment may constitute a very promising therapeutic modality for
these syndromes. Given the demonstrated role of cancer associated fibroblasts
(CAFs) in tumor progression and the putative CAFs features of some cancerprone
genodermatoses fibroblasts, in this study, we have further characterized
the phenotype of XP and GS dermal fibroblasts and evaluated their response to
methyl-δ-aminolevulinic acid (MAL)-PDT compared to that of dermal fibroblasts
obtained from healthy donors. We show here that XP/GS fibroblasts display clear
features of CAFs and present a significantly higher response to PDT, even after
being stimulated with UV light, underscoring the value of this therapeutic approach
for these rare skin conditions and likely to other forms of skin cancer were CAFs
play a major role